even asthma, leading to an average delay of almost
six years between the onset of symptoms and the
final diagnosis. 4
Although some patients present with normal
lung function at the time of diagnosis, AATD is
associated with increased risk of emphysema and
liver disease, namely cirrhosis and hepatocellular
carcinoma. Therefore, an early and correct diagnosis
may potentially enable an adequate monitoring of
these associated conditions, thus preventing further
tissue injury. 6
Better awareness by primary care providers,
who are most likely to be the first to interact with
patients with AATD, 7 can potentially be achieved
through continuing medical education and
dissemination of educational materials adapted to
both clinicians and patients. 5 General practitioners
might not always include AATD testing in the
assessment of COPD patients, and patients may
have to see more than one clinician before receiving
a correct diagnosis. 7 Reminders and warning
systems to physicians in electronic health records
that recommend testing for patients with specific
results in lung function tests, as well as clarification
of patient selection criteria for screening and
treatment and the
elimination of obstacles
regarding the laboratory
testing process (for
Analyses of patient registries in
example, distribution
different countries have shed light on
of free diagnostic kits,
screening campaigns)
the natural history of the disease and
the creation of
its diverse impact on long-term health and
incentives for testing,
status and QoL scores
can help overcome the
current challenges seen
in AATD diagnosis. 5
Health care policies and services can also pose
obstacles to uniform and equitable access to
care for AATD patients, hence the importance of
professional associations and regulatory entities in
the development of evidence-based and country-
appropriate clinical practice guidelines and health
policies having the ultimate goal of enabling the
collection of meaningful data and patient access to
existing and new cost-effective and safe therapies. 3
Impact of the disease on daily activities and
health-related QoL
Being a hereditary and progressively debilitating
disorder, AATD is necessarily associated with
the psychological burden of uncertainty about
prognosis, which can potentially result in worsening
of emotional and physical symptoms, depression
and/or anxiety, and overall reduction in quality of
life. 8 A cross-sectional study evaluated the role of
social environment for 462 patients with COPD
associated with AATD and showed that disease
uncertainty is reduced by higher quality of support
provided by families and social networks and the
availability of patient support groups, but increased
by having relatives with similar condition(s). 9
It is well known that patient-reported outcomes
such as health-related quality of life (HRQoL)
measures correlate with the extent of airway
obstruction and disease severity in COPD, and
they are now recognised as a relevant factor in the
evaluation of the disease’s burden because they
can accurately predict prognosis. 10,11 In AATD, high
exacerbation rates contribute to frequent absences
from work and physical limitations in performing
routine tasks, and smoking and occupational
exposure to dust and fumes can further contribute
to their increased frequency. 12
14 | 2019 | hospitalpharmacyeurope.com
Analyses of patient registries in different
countries have shed light on the natural history
of the disease and its diverse impact on long-term
health status and QoL scores. 3 In an analysis of 868
adult patients with severe AATD and asymptomatic
patients with a protease inhibitor ZZ genotype
(which represents the majority of patients with
AATD) included in the German AATD registry, data
collected over a period of seven years provided
important information about deterioration of
HRQoL as measured with the St George’s Respiratory
Questionnaire (SGRQ). Worsening of scores in the
SGRQ was significantly correlated with increased
frequency of annual self-reported exacerbations,
and significant correlations between SGRQ scores
at baseline with smoking habits and the diffusing
capacity of the lungs for carbon monoxide were
also observed. Moreover, a higher exacerbation rate
showed a greater effect specifically on the SGRQ
impact score, which assesses impact on employment
and daily activities, whereas smoking was strongly
associated with the physical activity component of
the assessment tool. 13
A large ongoing cross-sectional, prospective
study (NCT01245933; https://clinicaltrials.gov/
ct2/show/NCT01245933) involving 2741 patients
in the German COPD cohort COSYCONET aims
to determine the prevalence and severity of
extra-pulmonary conditions and their impact on
morbidity and mortality, including hospitalisation
rates. A comparative analysis of COPD patients
with or without AATD showed that presence of
AATD results in generic and disease-specific HRQoL
measures, as assessed by the SGRQ and the COPD
Assessment Test, that are similar to those of patients
without AATD despite lower overall health care
resource utilisation and medication burden. 14
Effect of AATD therapies on health status
The use of bronchodilators and corticosteroids
can effectively ameliorate dyspnoea and improve
exercise capacity, but these drugs do not actually
have an effect on the increased risk of emphysema
seen in patients with AATD. 4 Most of the treatment
options available for AATD are those also used
in patients having COPD, with the exception of
administration of weekly intravenous infusions
of purified Alpha 1 Antitrypsin (AAT) preparations,
obtained through the pooling of human plasma
from healthy donors. Such therapy has been shown
to slow lung function decline and organ damage in
several randomised and observational studies and is
suitable for patients with documented emphysema. 15
The evaluation of the clinical efficacy of AAT
therapy may be challenging when forced expiratory
volume and mortality are used as primary outcome
measures in clinical trials. Improvement in
exacerbations and survival rates have also been
used as efficacy endpoints, but they have lower
sensitivity than standard measures of pulmonary
function, and also requires long follow-up periods
and large sample sizes in order to adequately power
studies to detect significant differences, which is not
always feasible in AATD owing to the rarity of the
disease. In addition, prolonged use of the placebo
comparator raises concerns when an effective drug
is available on the market. 4,16
Despite its proven clinical benefits, treatment
is not curative but improves or stabilises the
irreversible process of loss of lung tissue and
the progression of emphysema. Regrettably,
the treatment is not available worldwide and is
relatively expensive, with total costs depending on
the patient’s body weight and on other factors such